The of the current research show that the insulin signaling pathways are up-regulated in the skin of normal subjects, in the wounded Cediranib AZD2171 skin of diabetic animals these upregulations are blunted. However, when the injured skin of diabetic rats is treated with an external insulin cream, a speed of wound-healing does occur, in association with a restoration in the proteins of the insulin signaling pathways. Our data show that the expression of proteins involved in early steps of insulin action, i. e., IR/IRS 1,2/AKT, are increased in the healing tissue of wounds, when compared with intact skin. AKT has got the ability to phosphorylate proteins that regulate lipid synthesis, glycogen synthesis, cell survival, and protein synthesis. Recently, information from different sources demonstrated that AKT activation is a significant step for VEGF release in skin wounds, through Immune system a post transcriptional device in keratinocytes, and is necessary for vascular growth and angiogenesis all through cutaneous wound-healing. Therefore, the increase in this signaling pathway observed in the healing skin of injuries might subscribe to the procedure for tissue repair in skin. Insulin activation of ERK involves the tyrosine phosphorylation of IRS proteins and/or SHC, which interact with the adapter protein, Grb2, getting the Son of sevenless exchange protein to the plasma membrane for activation of Ras. Once triggered, Ras works as a molecular switch, stimulating a serine kinase cascade through the stepwise activation of Raf, MEK, and ERK. Activated ERK can translocate into the nucleus, where it catalyzes the phosphorylation of transcription factors, initiating MAPK inhibitors a transcriptional program leading to cellular proliferation or differentiation. For that reason, we are able to suggest that the abnormal insulin signaling observed in damaged skin of diabetic subjects may possibly give rise to the impaired wound healing observed as a complication of diabetes. There are most likely several mechanisms that could attenuate insulin signaling within the skin of the diabetic. First, it is known that elevated levels of sugar influence insulin signaling by regulating the expression of a few genes, like the insulin receptor gene, at the transcriptional and translational levels. Moreover, hyperglycemia was demonstrated to inhibit insulin action as an outcome of serine phosphorylation of IRS via a PKC mediated process, that might subsequently increase the degradation of IRS proteins.